Organoid cultures derived from patients with advanced prostate cancer Academic Article uri icon

Overview

MeSH Major

  • Culture Techniques
  • Organoids
  • Prostatic Neoplasms

abstract

  • The lack of in vitro prostate cancer models that recapitulate the diversity of human prostate cancer has hampered progress in understanding disease pathogenesis and therapy response. Using a 3D organoid system, we report success in long-term culture of prostate cancer from biopsy specimens and circulating tumor cells. The first seven fully characterized organoid lines recapitulate the molecular diversity of prostate cancer subtypes, including TMPRSS2-ERG fusion, SPOP mutation, SPINK1 overexpression, and CHD1 loss. Whole-exome sequencing shows a low mutational burden, consistent with genomics studies, but with mutations in FOXA1 and PIK3R1, as well as in DNA repair and chromatin modifier pathways that have been reported in advanced disease. Loss of p53 and RB tumor suppressor pathway function are the most common feature shared across the organoid lines. The methodology described here should enable the generation of a large repertoire of patient-derived prostate cancer lines amenable to genetic and pharmacologic studies.

authors

publication date

  • September 25, 2014

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4237931

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2014.08.016

PubMed ID

  • 25201530

Additional Document Info

start page

  • 176

end page

  • 87

volume

  • 159

number

  • 1